The invention pertains to apparatus and method for non-invasively and quantitatively evaluating bone tissue in vivo, wherein the evaluation is manifested, at a given time, through one or more of the quantities: bone-mineral density, architecture, strength, and fracture-risk.
In recent years, various attempts have been made to use diverse forms of energy to assess the condition of bone tissue in vivo, but most often these attempts have been essentially ad hoc with no consistent framework within which to analyze data. In addition, the majority of the techniques employ signal-processing techniques that are so simple as to ignore available and useful aspects of the data; moreover, the signal-to-noise ratio of experimental data has been relatively poor. Perhaps most importantly, is that the prior techniques for bone characterization have utilized energy types for which the measurements (1) do not contain sufficient information to assess bone condition; (2) are affected significantly by non-bone related aspects (such as soft-tissue and musculature overlying the bone); (3) are subject to various measurement artifacts (such as transducer positioning, and pressure used when positioning the transducer); and/or (4) are relatively expensive to obtain.
Many prior techniques relied on ultrasonic measurements. Although significant information is obtainable from such data, ultrasound has not yet proved to be a useful tool for in vivo bone assessment. Ultrasonic techniques are highly sensitive to positioning of the transducers. Low-frequency vibrational measurements have also been proposed for assessing bone, but these have also not led to any practical clinical devices. In particular, vibrational measurements are strongly affected by soft tissue overlying the bone, as well as positioning and coupling the transducers to the skin.
Apparatuses which utilize ionizing electromagnetic radiation have also been developed and are currently used clinically to assess bone in vivo to provide estimates of bone mineral density. However these devices are relatively expensive, measure bone mass only (and not bone architecture, strength, and/or fracture risk), and expose the patient to ionizing radiation. A review of these radiation based methods may be found in the article by Ott et al., in the Journal of Bone and Mineral Research, Vol. 2, pp. 201-210, 1987.
Electrical (non-ionizing) impedance measurements have been applied for a variety of basic research purposes, but as of yet have apparently not been suggested as a means for clinical (in vivo) bone assessment in bone loss diseases, such as osteoporosis. Thus, we are disclosing for the first time method and apparatus for the use of non-ionizing electromagnetic measurements to assess bone in vivo, as a means for non-invasively determining the degree of osteoporosis in an individual, as represented by one or more of the following quantities: density, architecture, strength, and fracture risk.
U.S. Pat. No. 3,847,141 to Hoop discloses a device to measure bone density as a means of monitoring calcium content of the involved bone. A pair of opposed ultrasonic transducers is applied to opposite sides of a patient's finger, such that recurrent pulses transmitted via one transducer are "focused" on the bone, while the receiving response of the other transducer is similarly "focused" to receive pulses that have been transmitted through the bone. The circuitry is arranged such that filtered reception of one pulse triggers the next pulse transmission; the filtering is by way of a bandpass filter, passing components of received signals, only in the 25 to 125 kHz range; and the observed frequency of retriggering is said to be proportional to the calcium content of the bone.
Pratt, Jr. is identified with a number of U.S. patents, including U.S. Pat. No. 4,361,154, 4,421,119 (divisionally related to the '154 patent, and subsequently reissued, as Re. 32,782), U.S. Pat. Nos. 4,913,157, and 4,941,474, all dealing with establishing, in vivo, the strength of bone in a live being such as a horse. In the first three of his patents, the inventor bases his disclosures on the measurement of transit time from "launch" to "reception" of pulses of 0.5 MHz and 1.0 MHz through the bone and soft tissue, and from measurement of pulse-echo time, to thereby derive a measurement of transit time through bone alone. A data bank enables his evaluation of the meaning of variations in measurements of transit time, which the inventor deduces to be propagation velocity through each measured bone. The inventor's U.S. Pat. No. 4,913,157 operates on the same general principle of transit-time/velocity deduction, using the later preferred frequency of 2.25 MHz as the base frequency of pulsed "launchings", and he purports to derive the bone-transfer function from analysis of an average of received pulses. In his U.S. Pat. No. 4,941,474, the inventor further refines his technique of transit-time/velocity deduction, inter alia, by separately determining the ratio of the velocity of his observed "bone signal" to the velocity of his observed "soft-tissue signal", using the technique of matched filtering/Fourier transform filtering set forth in his U.S. Pat. No. 4,913,157.
Palmer, et al., U.S. Pat. No. 4,774,959 discloses apparatus for deriving the slope of the relation between ultrasonic frequency and attenuation, for the case of a sequence of tone signals, in the range 200 to 600 kHz, applied to one transducer and received by another transducer, (a) after passage through a heel bone, in comparison with (b) passage between the same two transducers without the intervening presence of the heel. The assumption necessarily is that the frequency/attenuation relation is a straight line, i.e. of constant slope.
Brandenburger, U.S. Pat. No. 4,926,870 discloses another in vivo bone-analysis system which depends upon measuring transit time for an ultrasonic signal along a desired path through a bone. A "Canonical" wave form, determined by previous experience to be on the correct path, is used for comparison against received signals for transmission through the patient's bone, while the patient's bone is reoriented until the received signal indicates that the patient's bone is aligned with the desired path. Again, ultrasonic velocity through the patient's bone is assumed to have been determined from measured transit time.
Rossman, et al., U.S. Pat. No. 5,054,490 discloses an ultrasound densitometer for measuring physical properties and integrity of a bone, upon determination of transit time, in vivo, through a given bone, in comparison with transit time through a medium of known acoustic properties; alternatively, the Rossman, et al. device compares absolute attenuation of specific frequency components of ultrasound acoustic signals through the bone with the absolute attenuation of the same frequency components through a medium of known acoustic properties. For attenuation measurements, a "broad-band ultrasonic pulse" is recommended and is illustrated as a single spike "which resonates with a broadband ultrasonic emission". The necessary comparisons are performed by a microprocessor, resulting in a slope of attenuation versus frequency in the broadband of interest. The frequencies or frequency ranges are not disclosed.
Kaufman et al., U.S. Pat. No. 5,259,384 disclose method and apparatus for ultrasonically assessing bone tissue. A composite sine wave acoustic signal consisting of plural discrete frequencies within the ultrasonic frequency range to 2 MHz are used to obtain high signal-to-noise ratio of the experimental data. A polynomial regression of the frequency-dependent attenuation and group velocity is carried out, and a non-linear estimation scheme is applied in an attempt to estimate the density, strength, and fracture risk of bone in vivo.
Doemland, U.S. Pat. No. 4,754,763 discloses a noninvasive system for testing the integrity of a bone in vivo. He uses low-frequency mechanical vibrations to characterize the state of healing in a fractured bone. The frequency response is used to classify the stage of healing.
Cain et al., U.S. Pat. No. 5,368,044 applied a similar method, namely, low-frequency mechanical vibrations, to assess the state or stiffness of bone in vivo. The method evaluates the peak frequency response or a cross-correlation of the frequency vs. amplitude response.
Brighton et al., U.S. Pat. No. 4,467,808 discloses method for preventing and treating osteoporosis in a living body by applying electrical stimulation non-invasively. They supply about 5-15 volts peak-to-peak at a single frequency within the range of about 20-100 kHz to cause a "treatment current" to flow in the bony part afflicted by osteoporosis.
Numerous other patents disclose methods for stimulating bone growth which rely on the application of electromagnetic signals to the body. For example, Ryaby et al. U.S. Pat. Nos. 4,105,017 and 4,315,503 describe methods for promoting bone healing in delayed and nonunion bone fractures, using an asymmetric pulsed waveform. In U.S. Pat. No. 4,993,413, McLeod et al. disclose method and apparatus for inducing a current and voltage in living tissue to prevent osteoporosis and to enhance new bone formation. They disclose the use of a symmetrical low frequency and low intensity electromagnetic signal substantially in the range of 1-1000 Hertz. In Liboff et al., U.S. Pat. No. 5,318,561 (and others), methods are disclosed which incorporate the combined use of a static and time-varying magnetic field to stimulate bone healing and growth. Specific amplitudes and frequencies are disclosed for optimal enhancement of bone growth, based on the theory of "ion-cyclotron resonance."
In several papers, including a review article, Saha et al. report on the electrical properties of bone. In "Electrical Properties of Bone," in Clinical Orthopaedics and Related Research, No. 186, June 1984, pp. 249-271, by Singh and Saha, they state that the electrical conductivity and permittivity of bone are frequency-dependent, reviewing data of various researchers in the 0-1 MHz frequency range. In two more recent papers, namely, "Electric and Dielectric Properties of Wet Human Cortical bone as a Function of Frequency," IEEE Transactions on Biomedical Engineering, Vol. 39, No. 12, December 1992, pp. 1298-1304, and "Electric and Dielectric Properties of Wet Human Cancellous Bone as a Function of Frequency," Annals of Biomedical Engineering, Vol. 17, pp. 143-158, 1989, both by Saha and Williams, they reported on the resistance and capacitance of in vitro bone samples in the frequency range 120 Hz to 10 MHz. They also studied the directional dependence of the measured impedance, and found that bone was electrically anisotropic. They also presented in vitro data on 30 cancellous bone samples which demonstrated a relatively small linear correlation (r=0.63) between specific capacitance and wet density.
The prior art, exemplified by the references that have been briefly discussed, have had little success in providing a simple, relatively inexpensive device or method for clinical non-invasive assessment of bone. They have focussed primarily on mechanical (low-frequency vibrational or ultrasonic) means, which thus far has not led to a useful clinical tool, or on much more expensive X-ray densitometers, which measure bone mass alone, with their associated ionizing radiation. On the contrary, electromagnetic measurements, although the subject of several academic in vitro investigations, have apparently been completely overlooked as a potential clinical tool for non-invasively assessing bone in vivo in bone loss diseases such as osteoporosis. In fact, the electrical parameters of bone have been investigated solely for their use in evaluating the currents and voltages induced by specific exogenous therapeutic or environmental electromagnetic fields. In the relatively few (in vitro) studies which considered the biophysical properties of bone in relation to electromagnetic measurements, no analytic framework was used, a broad frequency range was not used, and no attempt to develop a non-invasive clinical in vivo electromagnetic apparatus and/or method for assessing osteoporosis, with respect to bone-mineral density, architecture, strength and fracture risk, has previously been disclosed. There has also been a lack of effective methods for non-invasive assessment of materials and objects in general, not related only to bone.
Moreover, not only has the prior art been rather unsuccessful with respect to effective methods for diagnosis, but there has also been rather limited success in electromagnetic therapy of living tissues in general, and bone tissue in particular. This is notwithstanding the numerous attempts which have been made on this subject.